利用体外和计算机模拟方法鉴定水通道蛋白4抑制剂。

Identification of aquaporin 4 inhibitors using in vitro and in silico methods.

作者信息

Huber Vincent J, Tsujita Mika, Nakada Tsutomu

机构信息

Center for Integrated Human Brain Science, Brain Research Institute, University of Niigata, Chuo-ku, 1 Asahi Machi Dori, Niigata 951-8585, Japan.

出版信息

Bioorg Med Chem. 2009 Jan 1;17(1):411-7. doi: 10.1016/j.bmc.2007.12.040. Epub 2008 Jan 7.

DOI:10.1016/j.bmc.2007.12.040

PMID:18182301

Abstract

The in vitro inhibitory effects and in silico docking energies of 18 compounds with respect to aquaporin 4 (AQP4) were investigated. More than half of the compounds tested showed inhibitory activity in the in vitro functional assay and included the 5-HT(1B/1D) agonists sumatriptan, and rizatriptan. Moreover, the observed inhibitory activity of the compounds used in this study at 20 microM showed a strong correlation with their in silico docking energies, r(2)=0.64, which was consistent with that found in previous studies. The AQP4 inhibitory IC(50) values of three compounds, 2-(nicotinamido)-1,3,4-thiadiazole, sumatriptan and rizatriptan, were subsequently found to be 3, 11, and 2 microM, respectively.

摘要

研究了18种化合物对水通道蛋白4（AQP4）的体外抑制作用和计算机对接能。超过一半的受试化合物在体外功能试验中表现出抑制活性，其中包括5-HT(1B/1D)激动剂舒马曲坦和利扎曲坦。此外，本研究中使用的化合物在20微摩尔浓度下观察到的抑制活性与其计算机对接能呈强相关，r(2)=0.64，这与先前研究结果一致。随后发现三种化合物2-(烟酰胺基)-1,3,4-噻二唑、舒马曲坦和利扎曲坦的AQP4抑制IC(50)值分别为3、11和2微摩尔。